Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study.

Objective: To assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy.

Methods: Women diagnosed and treated for malignant ovarian germ cell tumors at Charing Cross Hospital or Mount Vernon Cancer Centre between 1977 and 2015 were included. Questionnaires assessing fertility issues were sent to patients treated with fertility-sparing surgery.

Can we replace adjuvant chemotherapy with surveillance for stage IA-C immature ovarian teratomas of any grade? an international multicenter analysis.

Background: The role of surveillance after surgery for stage IA-C grade 2 (G2) or grade 3 (G3) immature teratomas (ITs) is controversial with many guidelines advocating adjuvant chemotherapy. Here, we investigate the safety of surveillance in stage IA-C G1-3 ITs.

Methods: Clinicopathological data were analysed on postpubertal patients with stage I pure ITs in Multicenter Italian Trials in Ovarian Cancer centres and at Charing Cross Hospital, UK, between January 1985 and January 2018.

What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients.

Objective: To quantify the risk of developing post-molar gestational trophoblastic neoplasia (pGTN) beyond the first normal human chorionic gonadotrophin (hCG) in women who have had a complete (CHM) or partial molar pregnancy (PHM) and to re-evaluate the current UK Hydatidiform mole hCG surveillance guidelines.

Methods: The Charing Cross Hospital Trophoblast Disease Centre database was screened to identify all registered cases of hydatidiform mole (HM) between 1980 and 2009.

Results: We identified 20,144 cases of HM, comprising 8400 CHM, 9586 PHM, and 2158 cases of unclassified hydatidiform mole (UHM).

Chemical Transformations in Proto-Cytoplasmic Media. Phosphorus Coupling in the Silica Hydrogel Phase.

It has been proposed that prebiotic chemical studies on the emergence of primitive life would be most relevant when performed in a hydrogel, rather than an aqueous, environment. In this paper we describe the ambient temperature coupling of phosphorus oxyacids [Pi] mediated by Fe(II) under aerobic conditions within a silica hydrogel (SHG) environment. We have chosen to examine SHGs as they have considerable geological precedence as key phases in silicification to rock formation.

Power Doppler Quantification in Assessing Gestational Trophoblastic Neoplasia.

Purpose:  The FIGO score cannot accurately stratify low-risk gestational trophoblastic neoplasia (GTN) patients who develop chemoresistance to single agent methotrexate chemotherapy. Tumour vascularisation is a key risk factor and its quantification may provide non-invasive way of complementing risk assessment.

Materials And Methods:  187 FIGO-staged, low-risk GTN patients were prospectively recruited.

Anti-Müllerian Hormone in Patients Treated with Chemotherapy for Gestational Trophoblastic Neoplasia Does Not Predict Short-Term Fertility.

Objective: Serum anti-Müllerian hormone (AMH) is an emerging indicator of ovarian reserve which may be predictive of reproductive capacity. Although AMH levels decline with chemotherapy, little is known about the relevance of this to subsequent fertility, and we set out to evaluate this association in patients with gestational trophoblastic neoplasia (GTN).

Study Design: The GTN database of our national referral center was screened from 2008-2012 for patients undergoing AMH testing, and subsequent fertility outcomes were reviewed.

Atypical placental site nodule (APSN) and association with malignant gestational trophoblastic disease; a clinicopathologic study of 21 cases.

The WHO Classification of Gestational Trophoblastic Tumors classifies placental site nodule (PSN) as a benign tumor-like trophoblastic neoplasm. Cases of PSN with atypical features were described [atypical placental site nodule (APSN)] and we started registering APSN in our unit in 2005. The aim of this study is to present our initial experience with these lesions.

Effect of early pregnancy following chemotherapy on disease relapse and fetal outcome in women treated for gestational trophoblastic neoplasia.

Objective: To examine the effects of early pregnancy (< 12 months following chemotherapy) on a recent cohort of women treated with modern therapies for gestational trophoblastic neoplasia (GTN).

Study Design: The Charing Cross GTN database was screened between 1998-2012 to identify 1,204 patients treated with either single-agent (61.9%) or multiagent (38.

Management and survival of patients with FIGO high-risk gestational trophoblastic neoplasia: the U.K. experience, 1995-2010.

Objective: To present survival rates of high-risk gestational trophoblastic neoplasia (GTN) (FIGO score > 7) patients treated between 1995 and 2010 in the U.K. Death due to GTN is largely confined to patients with high-risk disease.

Antibody-peptide-MHC fusion conjugates target non-cognate T cells to kill tumour cells.

Attempts to generate robust anti-tumour cytotoxic T lymphocyte (CTL) responses using immunotherapy are frequently thwarted by exhaustion and anergy of CTL recruited to tumour. One strategy to overcome this is to retarget a population of virus-specific CTL to kill tumour cells. Here, we describe a proof-of-principle study using a bispecific conjugate designed to retarget ovalbumin (OVA)-specific CTL to kill tumour cells via CD20.

EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis.

Purpose: Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks).

Mutations in NLRP7 and KHDC3L confer a complete hydatidiform mole phenotype on digynic triploid conceptions.

Digynic triploidy is classically associated with a severely growth restricted fetus and a small nonmolar placenta. However, in genotyping hydatidiform moles as part of clinical practice, we identified two digynic triploid conceptions presenting with histopathological features of classical complete hydatidiform mole (CHM). Both cases occurred in women with a history of previous molar pregnancies and no normal pregnancies.

Survival of women with gestational trophoblastic neoplasia and liver metastases: is it improving?

Objective: To determine whether survival outcomes of women with liver metastases from gestational trophoblastic neoplasia (GTN) have improved from the previous finding of 27% at 5 years.

Study Design: The Charing Cross GTN database was searched for patients with liver metastases treated between 1975 and 2007. Prognostic variables were recorded and analyzed for effect on survival.

Mutations in NLRP7 are associated with diploid biparental hydatidiform moles, but not androgenetic complete moles.

Background: NLRP7 (NALP7) has been identified as the major gene involved in the inherited predisposition to recurrent molar pregnancies, a rare recessive condition in which affected individuals have complete hydatidiform moles of diploid biparental origin (BiCHM). The role of NLRP7 in other types of molar pregnancy and reproductive wastage has not been conclusively demonstrated. The purpose of this study was to clarify this by identifying NLRP7 variation in two clinically well-defined groups of patients: women with recurrent BiCHM, and women with three or more recurrent complete hydatidiform moles of proven androgenetic origin (AnCHM).

Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study.

Background: Indications for chemotherapy in gestational trophoblastic disease include raised human chorionic gonadotropin (hCG) concentrations 6 months after uterine evacuation of hydatidiform mole, even when values are falling. We aimed to establish whether chemotherapy is always necessary in these patients.

Methods: We retrospectively identified women registered between January, 1993, and May, 2008, at Charing Cross Hospital, London, UK, who had persistently high hCG concentrations 6 months after evacuation of hydatidiform mole.

667C>T and 1298A>C polymorphisms of MTHFR do not predict response to methotrexate in patients with gestational trophoblastic neoplasia.

Objective: Approximately one third of patients treated with methotrexate for gestational trophoblastic neoplasia (GTN) following a molar pregnancy are reported to develop resistance to methotrexate and need to change to different chemotherapeutic agents. Previous studies, in other clinical settings, have suggested that polymorphisms in key folate metabolising enzymes such as 5,10-methylenetetrahydrofolate reductase (MTHFR) influence both toxicity and efficacy of methotrexate. Our objective was to investigate the impact of two common functional MTHFR polymorphisms, 677C>T and 1298A>C, on the efficacy of methotrexate in women treated for GTN following a molar pregnancy.

Successful treatment of metastatic hepatic epithelioid hemangioendothelioma with thalidomide: a case report.

Introduction: Hepatic epithelioid hemangioendothelioma is a rare malignancy arising from the vascular endothelial cells within the liver. Historically, the disease is characterized as being poorly responsive to both chemotherapy and radiotherapy, with liver resection or transplantation the treatment of choice when feasible. For patients with advanced disease, reports of long-term therapeutic benefits from conventional cytotoxic treatments are very limited.

Differences in total human chorionic gonadotropin immunoassay analytical specificity and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors.

Objective: To determine the ability of several radioimmunoassays and commercial two-site immunoassays to detect the first World Health Organization International Reference Reagents (IRRs) for 6 defined human chorionic gonadotropin (hCG) variants and to compare their performance in measuring hCG in sera from patients with gestational trophoblastic disease (GTD) and germ cell tumors (GCTs) of the testis or ovary.

Study Design: The reactivity of the different assays with the 6 IRRs together with the current fourth International Standard (IS, 75/589) was tested using 5 commercial two-site assays as well as 2 competitive polyclonal radioimmunoassays (RIAs) and a competitive monoclonal immunoassay. Individual samples from 41 patients (19 GCT and 22 GTD) with high circulating levels of hCG (range, 718-6,055,000 IU/L) were diluted and measured using the various immunoassays.

Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.

Background: Placental-site trophoblastic tumours are a rare form of gestational trophoblastic disease and consequently information about optimum management or prognostic factors is restricted. We aimed to assess the long-term outcome of stage-adapted management by surgery, chemotherapy, or both for patients with the disorder.

Methods: 35 550 women were registered with gestational trophoblastic disease in the UK (1976-2006), of whom 62 were diagnosed with placental-site trophoblastic tumours and included, retrospectively, in the study.

Human chorionic gonadotropin free beta-subunit measurement as a marker of placental site trophoblastic tumors.

Objective: To evaluate the utility of free human chorionic gonadotropin beta-subunit (hCGbeta) proportion of total hCG measurement to distinguish placental site trophoblastic tumor (PSTT) from more common forms of gestational trophoblastic disease (GTD).

Study Design: Serum samples collected from PSTT, persistent trophoblastic disease (PTD) and choriocarcinoma patients were used for retrospective analysis of free hCGbeta-subunit. Results were reported as a percentage of total hCG using our in-house competitive radioimmunoassay.

Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome.

Objective: To evaluate the factors affecting outcome and the pathological findings in patients who had retroperitoneal lymph node dissection (pcRPLND) after chemotherapy with elevated tumour markers, as such patients have an unfavourable prognosis, with further salvage chemotherapy being the usual treatment of choice.

Patients And Methods: Information on the preoperative treatment, tumour markers, histopathology and outcome data of the patients who had pcRPLND were extracted from the hospital databases. Survival was analysed using the Kaplan-Meier method and multivariate analysis with Cox regression model.

The impact of molecular genetic diagnosis on the management of women with hCG-producing malignancies.

Objectives: The diagnosis of a gestational trophoblastic tumour (GTT) should be considered in all women presenting with a malignancy and an elevated human chorionic gonadotrophin (hCG) level. Whilst some non-gestational malignancies can also produce hCG, most non-gestational tumours can be distinguished from GTT on the basis of histopathological examination. However, some non-gestational tumours can exhibit trophoblastic differentiation and so make establishing the definitive diagnosis difficult.